We propose to study cultures of normal and neoplastic liver cells which are maintained in a state of growth or differentiation by specific culture conditions which include serum-free, hormonally defined media and substrata of tissue-specific extracellular matrix. These cultures of growing or differentiated liver cells will be characterized by Northern blot analysis for mRNA species for tissue-specific and housekeeping functions such as albumin, ligandin, transferrin, p450, actin and tubulin. The cultures also will be assessed for these functions by various protein or enzymatic assays. Comparisons will be made between the normal and neoplastic liver cells to ascertain what the distinctions are in their responses to hormones and/or extracellular matrix. We also will start the project of identifying and characterizing the tissue-specific and biologically active components in biomatrix. These studies in the chemical characterization of biomatrix are intended eventually to enable us to prepare substrata containing only the active components from the biomatrix, a goal which should improve even further our abilities to regulate the growth and differentiation of mammalian cells.